The problems of anesthetic drug action will be attacked in human, animal, and in vitro studies. Seventeen investigators form six interrelated teams working in four major areas: circulation, nerve and muscle, respiration, and neurophysiology. (1) Circulation: Dr. Bagshaw will study anesthetic effects on mechanisms of blood pressure control; regional hemodynamics will be measured as a function of carotid sinus pulse pressure, and again during infusion of sodium nitroprusside. Another group (Drs. Harp, Keykhah, Welsh, and Wollman) will study regional cerebral blood flow and cerebral metabolism during acid-base changes, hypotension, and head trauma. The protective effects of barbiturates and hypocapnia will be measured. (2) Nerve and muscle investigations (Drs. Rosenberg and Levitt) will include in vitro effects of anesthetics on metabolism, enzymes, and mechanics of skeletal muscle, and synaptosomes. Caffeine-induced contracture of frog and mammalian muscle will be used as a model of malignant hyperthermia. (3) In the respiratory area, a pulmonary pathophysiology group (Drs. Marshall, Neufeld, Aukburg, Geer, Klineberg, and Kennell) will study pulmonary injury due to multiple blood transfusions. Blood microaggregates, opsonins, capillary permeability, ventilation/perfusion inequality, and bronchial circulation will be part of these investigations. Pulmonary function of post-operative patients in intensive care will be assessed in several ways. A second group (Drs. Smith and Murphy) will investigate interactions of opioids, anesthetics, and premedicants on respiratory control, studying volunteers and patients. (4) Neurophysiology: Dr. Clark will continue studies of ischemic cerebral damage, collateral circulation, and protection by barbiturates and hypothermia. Investigators are supported by an analytical chemistry laboratory (Dr. Behar) and other shared core facilities, including major equipment and a well-equipped electronics laboratory.